ABSTRACT
Pulmonary arterial hypertension (PAH), formerly known as primary pulmonary hypertension (PPH), is a progressive disease characterized by widespread obstruction in the smallest pulmonary arteries. PAH may be heritable (HPAH), idiopathic (IPAH), or associated with other medical conditions or exposures to drugs or toxins. Familial cases have been recognized for the last half century and are usually due to mutations in the gene bone morphogenetic protein receptor type 2 (BMPR2), although in rare cases due to mutations in other members of the TGF-ß signaling family such as the genes that encode Smads. In addition, mutations in the TGF-β family genes activinlike kinase-type I (ALK1) and endoglin (ENG) are associated with hereditary hemorrhagic telangiectasia, which may have PAH in some cases. More recently, with the advent of next-generation sequencing, novel discoveries of genes associated with heritable pulmonary hypertension have been made, including caveolin-1 (CAV1), potassium channel 2-pore domain subfamily K member 3 (KCNK3), and eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4).
